The Comparative Pathology Core A will provide centralized pathology support for the three scientific projects and represents an evolution from the Mouse Pathobiology Core from the initial grant cycle. A major goal of the Comparative Pathology Core will be to provide expertise in mouse and human pathology with up-to-date proficiency in mammary gland and breast cancer pathology. In addition, a DVM, PhD postdoc in mouse pathology will perform the mouse necropsies (autopsies), cutting and processing of tissues, and evaluation of histopathology and special stains under the supervision of faculty pathologists. This will ensure excellence and continuity of service for the research projects. The Core will have 6 personnel that include three pathologists (one medical and two veterinary), medical oncologist (breast cancer specialist), a pathology fellow, and part-time histology technician. The Comparative Pathology Core is essential to ensure integration of the specific aims and experiments in relation to translation of the mouse genetic models to human breast cancer. The three pathologists and oncologist have a long track record of working together on collaborative projects, and therefore are well positioned to provide support for Core A. In addition, all three pathologists and the oncologist have collaborated with Drs. Ostrowski and Leone leading to shared authorship on manuscripts with high impact on mammary cancer microenvironment and its relationship to mammary cancer progression (1, 2). Facilities will include four necropsy rooms (including one devoted to mouse pathology), tissue processing facilities, histology laboratory with four full-time technicians (one devoted to the Core) and an automated Dako immunostainer. In Situ Molecular Pathology Core Lab with a Ventana staining system and NUANCE PLUS InForm computer-based analyses of co-expression of molecular targets, microscopy facilities including a 10-headed microscope with video output for conferences, laser capture microdissection facility and staff, tissue microarray laboratory, mouse imaging facilities including high resolution ultrasound, digital gross and microscopic photography, histomorphometry equipment including a fluorescent microscope and Image Pro Plus analysis software, and mouse surgery facilities. A SharePoint website will facilitate data transfer and sharing between the cores and project staff. These faculty and services will provide a unique resource to the research projects and significantly enhance the quality and validity of the research data.

Public Health Relevance

The comparative pathology core serves an integral link in the program grant to facilitate effective translation of molecular and tissue pathology in mouse models of mammary cancer to the pathogenesis and prognosis of breast cancer in women particularly as it relates to epithelial and stromal interactions. The team of veterinary and medical pathologists specialize in mammary cancer and have the laboratory resources and personnel to support the objectives of the core and program grant.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-O (O1))
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Ohio State University
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Rudolph, M; Sizemore, S T; Lu, Y et al. (2018) A hedgehog pathway-dependent gene signature is associated with poor clinical outcomes in Luminal A breast cancer. Breast Cancer Res Treat 169:457-467
Sizemore, Gina M; Balakrishnan, Subhasree; Thies, Katie A et al. (2018) Stromal PTEN determines mammary epithelial response to radiotherapy. Nat Commun 9:2783
Sizemore, Steven T; Mohammad, Rahman; Sizemore, Gina M et al. (2018) Synthetic Lethality of PARP Inhibition and Ionizing Radiation is p53-dependent. Mol Cancer Res 16:1092-1102
Pitarresi, Jason R; Liu, Xin; Avendano, Alex et al. (2018) Disruption of stromal hedgehog signaling initiates RNF5-mediated proteasomal degradation of PTEN and accelerates pancreatic tumor growth. Life Sci Alliance 1:e201800190
Ahirwar, Dinesh K; Nasser, Mohd W; Ouseph, Madhu M et al. (2018) Fibroblast-derived CXCL12 promotes breast cancer metastasis by facilitating tumor cell intravasation. Oncogene 37:4428-4442
Victor, Aaron R; Nalin, Ansel P; Dong, Wenjuan et al. (2017) IL-18 Drives ILC3 Proliferation and Promotes IL-22 Production via NF-?B. J Immunol 199:2333-2342
Liu, Huayang; Dowdle, James A; Khurshid, Safiya et al. (2017) Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation. Dev Cell 41:392-407.e6
Tang, Xing; Srivastava, Arunima; Liu, Huayang et al. (2017) annoPeak: a web application to annotate and visualize peaks from ChIP-seq/ChIP-exo-seq. Bioinformatics 33:1570-1571
Sizemore, G M; Balakrishnan, S; Hammer, A M et al. (2017) Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1. Oncogene 36:2297-2308
Hammer, Anisha M; Sizemore, Gina M; Shukla, Vasudha C et al. (2017) Stromal PDGFR-? Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth. Neoplasia 19:496-508

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